BACKGROUND: Aquaporin-4 (AQP-4), which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain in...BACKGROUND: Aquaporin-4 (AQP-4), which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown. OBJECTIVE: To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin (AVP). DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS: Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS: A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points: 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES: Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS: Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema (r= 0.870, 0.848, P 〈 0.01). CONCLUSION: AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.展开更多
BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270...BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.展开更多
The vascular reactivity and calcium sensitivity were decreased following hemorrhagic shock.Arginine vasopressin(AVP)was beneficial to endotoxic,infec-tious/septic and hemorrhagic shock.Our previous studies found that ...The vascular reactivity and calcium sensitivity were decreased following hemorrhagic shock.Arginine vasopressin(AVP)was beneficial to endotoxic,infec-tious/septic and hemorrhagic shock.Our previous studies found that Rho kinase played an important role in the occurrence of calcium desensitization following shock.It was reported that AVP was with stimulation effect of Rho kinase.So we hypothesized that AVP might have bene-ficial effect on shock via activation of Rho kinase to regu-late the calcium sensitivity and vascular reactivity.Hemorrhagic shock(40 mmHg for 2 h)Wistar rats in vivo were adopted to observe the effects of small dose of AVP on hemodynamics,24-h survival rate,the pressor effect of norepinephrine(NE)and the contractility of superior mesenteric artery(SMA).Isolated SMAs from hemorrha-gic shock rats were adopted to observe the effects of AVP on vascular reactivity and calcium sensitivity and its rela-tionship to Rho kinase with an isolated organ perfusion system.The results show that AVP at the concentration of 0.1 U/kg and 0.4 U/kg significantly improved the hemo-dynamic parameters and the 24-h survival rate of hemor-rhagic shock rats.Meanwhile,these dosages of AVP significantly increased the pressor effect of NE and the contractile response of SMA to NE.Y-27632(3 mg/kg),a Rho kinase specific inhibitor,abolished the beneficial effects of AVP.In vitro,the calcium sensitivity and vas-cular reactivity of SMA to calcium and NE were signifi-cantly decreased following hemorrhagic shock.AVP at the concentration of 0.5 nmol/L and 5 nmol/L signifi-cantly increased the calcium sensitivity and vascular react-ivity.These effects of AVP were abolished by Y-27632(10 mmol/L).Taken together,the results suggest that AVP at 0.1 U/kg and 0.4 U/kg is beneficial to hemorrha-gic shock by improving the vascular reactivity,which involves activation of Rho kinase.展开更多
A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine...A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS, and biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, It and 1v exhibited excellent diuretic activity, especially 1 r and 1v. Therefore, 1 r and 1v are potent novel AVP V2 receptor antagonist candidates.展开更多
Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, ...Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.展开更多
BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE...BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed (P 〈 0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.展开更多
BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vaso...BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.展开更多
The purpose of this study was to investigate the effect of nonadrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2(ETCO2)during CPR in a rodent model. Our results suggested that: 1) coronary perf...The purpose of this study was to investigate the effect of nonadrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2(ETCO2)during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension- Ⅱ(ANG- Ⅱ), but not by endothelin-1 (ET-1): 2) ETCO2 prior to defibrillation was decreased significantly by a pure a1 adrenergic agents,methoxamine and were increased significantly by non-adrenergic agents, ANG-Ⅱ and ET-1 during rodent CPR;3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-Ⅱ have similar effect on resuscitability during rodent CPR.展开更多
The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that proje...The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3–6 days after injecting a retrograde tracer pseudorabies virus(PRV)-614 into kidney of 13 adult male C57BL/6J strain mice. PRV-614 infected neurons were detected in a number of mesencephalic(e.g. central amygdala nucleus), telencephalic regions and motor cortex. These divisions included the preoptic area(POA), dorsomedial hypothalamus(DMH), lateral hypothalamus, arcuate nucleus(Arc), suprachiasmatic nucleus(SCN), periventricular hypothalamus(Pe H), and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus(PVN). PRV-614/Tyrosine hydroxylase(TH) double-labeled cells were found within DMH, Arc, SCN, Pe H, PVN, the anterodorsal and medial POA. A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic. PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin. These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.展开更多
Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi....Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.展开更多
Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities w...Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.展开更多
Objective To investigate the antipyretic effect of Eupatorium chinense and its mechanism. Methods The content of arginine vasopressin(AVP) in ventral septal area(VSA) and blood plasma, and cyclic adenosine monopho...Objective To investigate the antipyretic effect of Eupatorium chinense and its mechanism. Methods The content of arginine vasopressin(AVP) in ventral septal area(VSA) and blood plasma, and cyclic adenosine monophosphate(c AMP) levels of hypothalamus and blood plasma were determined by enzyme linked immunosorbent assay. Results The body temperature(Tb) was decreased at 1 h after administration of E. chinense(3 and 6 g/kg) and Aspirin(0.3 g/kg) respectively, which was significantly different from the temperature of fever model group. The antipyretic effect of Aspirin and E. chinense lasted for longer time. Aspirin(0.3 g/kg) and E. chinense(3 and 6 g/kg)reduced the level of cA MP in hypothalamus of fever rats and increased AVP content in plasma. The changes in c AMP content in plasma of all drug treatment groups were not obvious. Conclusion E. chinense has strong antipyretic effect and may affect the production of AVP and c AMP in fever rats.展开更多
基金the National Natural Science Foundation of China, No. 30470608, 30500171
文摘BACKGROUND: Aquaporin-4 (AQP-4), which is able to rapidly transport water within the brain, is highly expressed in brain tissue. It also plays an important role in the formation of cerebral edema following brain injury. However, the role of AQP-4 in the formation of cerebral edema following severe bums remains unknown. OBJECTIVE: To study changes in AQP-4 protein and mRNA expression during formation of cerebral edema following severe burns, and to explore the correlation between AQP-4 protein and mRNA expression with plasma levels of arginine vasopressin (AVP). DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Research Center of Neuroscience, Chongqing Medical University from 2007 to 2008. MATERIALS: Biotin-labeled goat anti-rabbit antibody was provided by Beijing Zhongshan Biotechnology, China; in situ hybridization kit was provided by Wuhan Boster Biotechnology, China; rabbit anti-AQP-4 polyclonal antibody and horseradish peroxidase-labeled goat anti-rabbit IgG were provided by Chemicon, USA; AVP radioimmunoassay kit was provided by the Research Department of Neurobiology, the Second Military Medical University of Shanghai, China. METHODS: A total of 180 adult, healthy, Wistar rats were randomly assigned to control and burn groups with 30 rats in each group. The burn group was observed at five different time points: 2, 6, 12, 24, and 48 hours after burn. Hair on the mouse back was removed to expose skin on the back. After 1 day, skin with the hair removed was dipped into 100℃ water for 15 seconds to induce grade III bum injury that measures 30% of total bum surface area. MAIN OUTCOME MEASURES: Brain water content was measured using the dry-wet weight method. AQP-4 protein and mRNA expressions were detected using immunohistochemistry, in situ hybridization, Western blot, and reverse transcription-polymerase chain reaction; dynamic changes in plasma AVP were detected using radioimmunoassay. RESULTS: Brain water content gradually increased following severe burn injury. AQP-4 protein and mRNA expressions were upregulated in the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, hippocampus, choroid plexus, and cerebral cortex. Plasma AVP levels increased following burn injury. AQP-4 protein and mRNA expressions positively correlated with brain water content and AVP levels during formation of cerebral edema (r= 0.870, 0.848, P 〈 0.01). CONCLUSION: AQP-4 participated in the formation of cerebral edema following burn injury. Plasma AVP upregulated AQP-4 expression in brain tissue, thereby promoting formation of cerebral edema.
文摘BACKGROUND Congenital nephrogenic diabetes insipidus(CNDI)is a rare hereditary disorder.It is associated with mutations in the arginine vasopressin receptor 2(AVPR2)gene and aquaporin 2(AQP2)gene,and approximately 270 different mutation sites have been reported for AVPR2.Therefore,new mutations and new manifestations are crucial to complement the clinical deficiencies in the diagnosis of this disease.We report a case of a novel AVPR2 gene mutation locus and a new clinical manifestation.CASE SUMMARY We describe the case of a 48-d-old boy who presented with recurrent fever and diarrhea 5 d after birth.Laboratory tests showed electrolyte disturbances and low urine specific gravity,and imaging tests showed no abnormalities.Genetic testing revealed a novel X-linked recessive missense mutation,c.283(exon 2)C>T(p.P95S).This mutation results in the substitution of a proline residue with a serine residue in the AVPR2 protein sequence.The diagnosis of CNDI was confirmed based on the AVPR2 gene mutation.The treatment strategy for this patient was divided into two stages,including physical cooling supplemented with appropriate amounts of water in the early stage and oral hydrochlorothiazide(1-2 mg/kg)after a clear diagnosis.After follow-up of one and a half years,the patient gradually improved.CONCLUSION AVPR2 gene mutations in new loci and new clinical symptoms help clinicians understand this disease and shorten the diagnosis cycle.
基金supported by the National Natural Science Foundation of China(Grant Nos.30600228 and 30625037)the National Basic Research Program of China(2005CB522601)the Innovation Group Plan of Ministry of Education(IRT0712).
文摘The vascular reactivity and calcium sensitivity were decreased following hemorrhagic shock.Arginine vasopressin(AVP)was beneficial to endotoxic,infec-tious/septic and hemorrhagic shock.Our previous studies found that Rho kinase played an important role in the occurrence of calcium desensitization following shock.It was reported that AVP was with stimulation effect of Rho kinase.So we hypothesized that AVP might have bene-ficial effect on shock via activation of Rho kinase to regu-late the calcium sensitivity and vascular reactivity.Hemorrhagic shock(40 mmHg for 2 h)Wistar rats in vivo were adopted to observe the effects of small dose of AVP on hemodynamics,24-h survival rate,the pressor effect of norepinephrine(NE)and the contractility of superior mesenteric artery(SMA).Isolated SMAs from hemorrha-gic shock rats were adopted to observe the effects of AVP on vascular reactivity and calcium sensitivity and its rela-tionship to Rho kinase with an isolated organ perfusion system.The results show that AVP at the concentration of 0.1 U/kg and 0.4 U/kg significantly improved the hemo-dynamic parameters and the 24-h survival rate of hemor-rhagic shock rats.Meanwhile,these dosages of AVP significantly increased the pressor effect of NE and the contractile response of SMA to NE.Y-27632(3 mg/kg),a Rho kinase specific inhibitor,abolished the beneficial effects of AVP.In vitro,the calcium sensitivity and vas-cular reactivity of SMA to calcium and NE were signifi-cantly decreased following hemorrhagic shock.AVP at the concentration of 0.5 nmol/L and 5 nmol/L signifi-cantly increased the calcium sensitivity and vascular react-ivity.These effects of AVP were abolished by Y-27632(10 mmol/L).Taken together,the results suggest that AVP at 0.1 U/kg and 0.4 U/kg is beneficial to hemorrha-gic shock by improving the vascular reactivity,which involves activation of Rho kinase.
基金supported by National Major Scientific and Technological Special Project for "Significant New Drugs Development"(Nos.2011ZX09401-009 and 2013ZX09102014)
文摘A series of novel phenothiazine derivatives was synthesized and tested for arginine vasopressin receptor antagonist activity. They were synthesized as novel arginine vasopressin receptor antagonists from phenothiazine as a scaffold via successive acylation, reduction and acylation reactions. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS, and biological activity was evaluated by in vitro and in vivo studies. The in vitro binding assay indicated that several compounds are potent selective V2 receptor antagonists. Compounds with promising binding affinity to V2 receptors were selected to conduct the in vivo diuretic studies on Sprague-Dawley rats. Among them, 1n, 1r, It and 1v exhibited excellent diuretic activity, especially 1 r and 1v. Therefore, 1 r and 1v are potent novel AVP V2 receptor antagonist candidates.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515011371 (to JP),2021A1515110290 (to YO),2020A1515110564 (to XW)2023A 1 515010150 (to MZ)+2 种基金Science and Technology Planning Project of Guangzhou,No.202102020977 (to ZF)the National Natural Science Foundation of China,Nos.82201516 (to YO) and 81900709 (to ZF)President Foundation of Nanfang Hospital,Southern Medical University,Nos.2019C001 (to MZ),2019C016 (to XW), 2021C045 (to YO)。
文摘Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.
基金the Postdoctoral Science Foundation of China,No. 20060390301the National Natural Science Foundation of China,No.30600341the Ph.D.Program Foundation of Ministry of Education of China,No.20050159011
文摘BACKGROUND: The hippocampus regulates the hypothalamic-pituitary-adrenal axis through negative feedback. The hypothalamic paraventricular nucleus receives neuronal input from the hippocampus via the fomix, OBJECTIVE: To explore whether the negative feedback effect of the hippocampus on the hypothalamic-pituitary-adrenal axis is contributed to the inhibitory effect of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus on the paraventricular nucleus via the fornix. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at the Department of Histology and Embryology, China Medical University between September 2006 and September 2008. MATERIALS: Rabbit anti-rat anti-MR and rabbit anti-rat anti-GR antibodies were purchased from Santa Cruz Biotechnology, USA. Rabbit anti-rat anti-corticotrophin releasing hormone (CRH) and rabbit anti-rat anti-arginine vasopressin antibodies were purchased from Wuhan Boster. METHODS: A total of 90 male, Wistar rats were randomly divided into model and sham-surgery groups (n = 45). Fornix transection was performed in the model group, while the sham-surgery group underwent surgery, but no fornix transection. MAIN OUTCOME MEASURES: Immunohistochemistry was used to examine MR and GR expression in the hippocampus, as well as CRH and anti-arginine vasopressin in the paraventricular nucleus. Western blot was used to measure alterations in MR, GR, and CRH protein expression following fomix transection. RESULTS: Compared with the sham-surgery group, there were no obvious changes in MR and GR expression in the hippocampus, or CRH and anti-arginine vasopressin expression in the paraventdcular nucleus within 4 days of fornix transection. However, after 7-10 days, significantly decreased MR and GR expression in the hippocampus, and increased CRH and anti-arginine vasopmssin expression in the paraventricular nucleus were observed (P 〈 0.05-0.01). CONCLUSION: Negative feedback from the hippocampus on the hypothalamic-pituitary-adrenal axis might be mediated through the fornix, and the corticosterene actions mediated by hippocampal corticosteroid receptors indirectly modulated the hypothalamic-pituitary-adrenal axis.
文摘BACKGROUNDVasoplegic shock is a challenging complication of cardiac surgery and is oftenresistant to conventional therapies for shock. Norepinephrine and epinephrine arestandards of care for vasoplegic shock, but vasopressin has increasingly been usedas a primary pressor in vasoplegic shock because of its unique pharmacology andlack of inotropic activity. It remains unclear whether vasopressin has distinctbenefits over standard of care for patients with vasoplegic shock.AIMTo summarize the available literature evaluating vasopressin vs non-vasopressinalternatives on the clinical and patient-centered outcomes of vasoplegic shock inadult intensive care unit (ICU) patients.METHODSThis was a systematic review of vasopressin in adults (≥ 18 years) with vasoplegicshock after cardiac surgery. Randomized controlled trials, prospective cohorts,and retrospective cohorts comparing vasopressin to norepinephrine, epinephrine,methylene blue, hydroxocobalamin, or other pressors were included. The primaryoutcomes of interest were 30-d mortality, atrial/ventricular arrhythmias, stroke,ICU length of stay, duration of vasopressor therapy, incidence of acute kidneyinjury stage II-III, and mechanical ventilation for greater than 48 h.RESULTSA total of 1161 studies were screened for inclusion with 3 meeting inclusioncriteria with a total of 708 patients. Two studies were randomized controlled trials and one was a retrospective cohort study. Primary outcomes of 30-d mortality,stroke, ventricular arrhythmias, and duration of mechanical ventilation weresimilar between groups. Conflicting results were observed for acute kidney injurystage II-III, atrial arrhythmias, duration of vasopressors, and ICU length of staywith higher certainty of evidence in favor of vasopressin serving a protective rolefor these outcomes.CONCLUSIONVasopressin was not found to be superior to alternative pressor therapy for any ofthe included outcomes. Results are limited by mixed methodologies, small overallsample size, and heterogenous populations.
文摘The purpose of this study was to investigate the effect of nonadrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2(ETCO2)during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension- Ⅱ(ANG- Ⅱ), but not by endothelin-1 (ET-1): 2) ETCO2 prior to defibrillation was decreased significantly by a pure a1 adrenergic agents,methoxamine and were increased significantly by non-adrenergic agents, ANG-Ⅱ and ET-1 during rodent CPR;3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-Ⅱ have similar effect on resuscitability during rodent CPR.
文摘The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3–6 days after injecting a retrograde tracer pseudorabies virus(PRV)-614 into kidney of 13 adult male C57BL/6J strain mice. PRV-614 infected neurons were detected in a number of mesencephalic(e.g. central amygdala nucleus), telencephalic regions and motor cortex. These divisions included the preoptic area(POA), dorsomedial hypothalamus(DMH), lateral hypothalamus, arcuate nucleus(Arc), suprachiasmatic nucleus(SCN), periventricular hypothalamus(Pe H), and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus(PVN). PRV-614/Tyrosine hydroxylase(TH) double-labeled cells were found within DMH, Arc, SCN, Pe H, PVN, the anterodorsal and medial POA. A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic. PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin. These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.
文摘Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.
基金project was supported by National 973 Plan(Nos. 2010CB735602 and 2012CB724002)National Major Scientific and Technological Special Project for "Significant New Drugs Development"(No.2011ZX09401-009)
文摘Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.
文摘Objective To investigate the antipyretic effect of Eupatorium chinense and its mechanism. Methods The content of arginine vasopressin(AVP) in ventral septal area(VSA) and blood plasma, and cyclic adenosine monophosphate(c AMP) levels of hypothalamus and blood plasma were determined by enzyme linked immunosorbent assay. Results The body temperature(Tb) was decreased at 1 h after administration of E. chinense(3 and 6 g/kg) and Aspirin(0.3 g/kg) respectively, which was significantly different from the temperature of fever model group. The antipyretic effect of Aspirin and E. chinense lasted for longer time. Aspirin(0.3 g/kg) and E. chinense(3 and 6 g/kg)reduced the level of cA MP in hypothalamus of fever rats and increased AVP content in plasma. The changes in c AMP content in plasma of all drug treatment groups were not obvious. Conclusion E. chinense has strong antipyretic effect and may affect the production of AVP and c AMP in fever rats.